title: Intracellular pH-sensitive PEG-block-acetalated-dextrans as efficient drug delivery platforms.
abstract: Intracellular pH-sensitive micelles of PEG-block-acetalated-dextran (PEG-b-AC-Dex) were prepared and used for acid-triggered intracellular release of anticancer drug. The hydrodynamic radii (Rh) of PEG-b-AC-Dex micelles could increase after incubation in PBS solution at pH 5.5. Based on the pH-responsive Rh variation behavior, it was expected that the PEG-b-AC-Dex micelles should be interesting for intracellular drug delivery. Thus, doxorubicin (DOX), a wide-spectrum anticancer drug, was loaded into the micelles and the pH-dependent release of the payload DOX was tested in vitro. The in vitro drug release profiles showed that only a small amount of the loaded DOX was released in PBS solution at pH 7.4, while up to about 90% of the loaded DOX could be quickly released in PBS solution at pH 5.5. Compared to pH-insensitive PEG-PLA micelles, the PEG-b-AC-Dex micelles displayed a faster drug release behavior in tumor cells. Moreover, higher cellular proliferation inhibition efficacy was achieved toward tumor cells. These features suggested that DOX could be efficiently loaded and delivered into tumor cells in vitro by the intracelluar pH-sensitive micelles, leading to enhanced inhibition of tumor cell proliferation. Therefore, the pH-sensitive micelles may provide a promising carrier for acid-triggered drug release for cancer therapy.
authors.affiliation: Department of Chemistry, Northeast Normal University , Changchun 130024, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Shuangjiang
authors.initials: S
authors.lastname: Yu
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.forename: Chaoliang
authors.initials: C
authors.lastname: He
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D011108:Polymers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D004317:Doxorubicin